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Health Library

The Health Library at Vista Center is an affiliate of Stanford Hospital Health Library.

The Health Library  is designed to help address the needs of individuals with vision loss, with comprehensive information about:

The library is staffed by visually impaired volunteers Health Library Volunteer conversing with clienttrained in researching health-related questions. Our volunteers are equipped to provide information, not medical advice. Although they are happy to help clients by researching  questions, we recommend that users contact their doctor or other health care professional when medical advice is needed.

The Health Library  produces three e-mail research lists:

These newsletters are compiled of research reports and excerpts from professional sources including Medline, Medscape, Nature and ophthalmology journals.

Individual health and medical information requests will be searched for and the results sent in large print, cd txt or MP3, braille or e-mail.   

Yearly updated packets of information are available about macular degeneration, glaucoma, diabetic retinopathy and others. Some are available in Spanish.  Our services are provided free to anyone in the blind and visually impaired community. E-mail or call the Health Library with your requests at 650-858-0202 Extension 132. thl@vistacenter.org 

The Eye, a Verbal Description (MP3)

Braving the Low Vision Exam (MP3)

Medical News Articles

Stem cell secretions may protect against glaucoma

GLAUCOMA NIH 1/27/17: Stem cell secretions may protect against glaucoma - A new study in rats shows that stem cell secretions, called exosomes, appear to protect cells in the retina.  The findings point to potential therapies for glaucoma, a leading cause of blindness in the US. Exosomes are tiny membrane-enclosed packages that form inside of cells before getting expelled. Long thought of as part of a cellular disposal system, scientists have recently discovered that exosomes are packed with proteins, lipids and gene-regulating RNA. Studies have shown that exosomes from one cell can be taken up by another by fusing with the target cell’s membrane, spurring it to make new proteins. Ben Mead, PhD at NEI, and team investigated the role of stem cell exosomes on retinal ganglion cells (RGC) a type of retinal cell that forms the optic nerve that carries visual information from the eye to the brain. The death of RGCs leads to vision loss in glaucoma and other optic neuropathies. *
More...Stem cells have been the focus of therapeutic attempts to replace or repair tissues because of their ability to morph into any type of cell in the body. However, from a practical standpoint, using exosomes isolated from stem cells has some key advantages over transplanting whole stem cells. “Exosomes can be purified, stored and precisely dosed in ways that stem cells cannot,” Dr. M said.  Another important advantage is that exosomes  lack the risks associated with transplanting live stem cells into the eye, which can potentially lead to complications such as immune rejection and unwanted cell growth.  Mead used a rat glaucoma model to study the effects of exosomes isolated from bone marrow stem cells on RGCs.         Exosomes were injected weekly into the rats’ vitreous, the fluid within the center of the eye. Prior to injection, the exosomes were fluorescently labelled allowing the team to track the delivery of the exosome cargo into the RGCs. The exosome-treated rats lost about a third of their RGCs following optic nerve injury, versus a 90% loss among untreated rats. The treated RGCs also maintained function, according to electroretino-graphy, which measures electrical activity of retinal cells.  The team found that the protective effects of exosomes are regulated by microRNA, molecules that interfere with or silence gene expression. Further research is needed said S Tomarev, PhD coauthor.  We need to know which particular microRNA are involved and what proteins are being targeted upon arrival, he said  Finally, the most optimal exosome approach needs to be found. A lot will depend on how frequently exosomes need to be administered to achieve a therapeutic effect. Ref: Mead, B. and Tomarev S(2017)... Stem Cells Translational Medicine. NIH News 1/27/17

AMD-RETINA: FDA Grants VisionCare Approval to Initiate Clinical Study of the Telescope Implant in Patients After Cataract Surgery: 

The study will evaluate the safety and effectiveness of the telescope implant in patients who were previously implanted with an intra ocular lens (IOL). In the study, the IOL will be exchanged for the Implantable Miniature Telescope (by Dr. Isaac Lipshitz). Under current indications the telescope implant is proven to improve visual acuity and quality of life for patients with end-stage macular degeneration whose sight is permanently obstructed by a blind spot in their central vision (in both eyes), making it difficult or impossible to see faces, read, and perform everyday activities such as watching TV, preparing meals, and self-care. It is the only FDA approved surgical device for end-stage macular degeneration and is Medicare eligible.  According to current labeling, the telescope implant is contraindicated in patients with previous intraocular or corneal surgery of any kind in the operative eye, including any type of surgery for either refractive or therapeutic purposes. Specifically, the new study will evaluate the safety and effectiveness of the telescope implant in patients who were previously implanted with an intraocular lens. * more..Selected CentraSight providers across the country are now seeking end-stage macular degeneration patients with previous cataract surgery to determine if they might be candidates as study subjects for the telescope implant.   "Cataract surgery is often performed on patients living with macular degeneration in the hopes that an IOL will improve contrast and light. However, studies show that these patients do not experience an appreciable improvement in their visual acuity, post cataract surgery," Stephen Lane, MD, said in the news release. "The long term efficacy of the telescope implant in improving vision and quality of life in AMD patients has been demonstrated during studies that followed subjects up to 8 years post-surgery. This study will inform us about the safety, effectiveness, and the appropriate surgical technique for implanting the telescope in patients who have had cataract surgery before."  Hundreds of patients have experienced the CentraSight treatment program and learned to use their new, improved vision, effectively," B Michaels, CEO of VisionCare, said "We hope the results of this study will allow us to offer the telescope implant to an even broader population of patients who are currently excluded simply because they had a routine eye surgery in the past.  Source VisionCare; EyeWire 1/12/17

DIABETES 1/26/17: Bariatric Surgery May Help Diabetes, But What About  Retinopathy?

Expert Critique  Krista Gonzales MD  Endocrinology Fellow   Bariatric surgery (BS), a promising treatment option for  diabetes, has other advantages which have not yet been  fully explored. One such advantage includes possible stabilization of diabetic retinopathy (DR).  The Diabetes Control and Complications trial revealed the adverse short-term (less than 2 years) and favorable longer-term effects of intensive medical management on retinopathy. The UK Prospective Diabetes Study showed that tight glycemic control was associated with protection from DR and other microvascular (very small vessel)  complications.   Two meta-analyses explore the benefit-to-risk ratio of  BS  on diabetic retinopathy progression  versus reduction. These studies demonstrate concern for greater early worsening of DR risk in surgical patients rather than those on medical  therapy.    The first study concluded that there was no greater protection from bariatric surgery against DR, in those without retinopathy at baseline. The second study found that the most common outcome was the absence of any change, regression or progression.  Hence, a stabilizing effect was supported by both studies.  The impact of BS on the risk of development or progression of diabetic retinopathy remains unresolved.*    more...Two recently published reviews  addressed this question.   In one, pooled data from 876 patients found the odds ratio for diabetic progression among patients who underwent BS relative to those managed with medical treatment alone was 0.47. However, there was no greater protection against DR in those didn't have retinopathy  before the procedure. In a separate meta-analysis, conducted in patients with sight-threatening diabetic retinopathy at baseline, no significant protection from progression was observed.  The studies ranged from 22 to 15,951 patients with follow-up of 6 months to 5 years. The most common outcome observed in all studies was the absence of any change. The messages from both the recent meta-analysis and the review are different but not necessarily inconsistent. - The author of this cohort  study, A A Tahrani, UK, cautioned that rigorously match-controlled or even randomized trials may not, by themselves, resolve all the issues.  "Animal studies  would be crucial to explain the interaction between  different mechanisms that might affect DR following bariatric surgery such as the impact of  hyperglycemia, diabetes remission, the rapidity of glycemic improvement, and the effects of postprandial  hypoglycemia," He believes that it is  important to consider outcomes separately for those who  have or do not have diabetic retinopathy at the time of  surgery.  R P. Singh, MD, Cleveland Clinic's Cole Eye Institute agreed that the definitive study has yet to be conducted. Endocrine Society Reading Room 1/25/17 Medpage 1/26/17

How eyes sense motion

Nature 5/4  Wiring of retina reveals how eyes sense motion A vast project to map neural connections in the mouse retina may have answered the question of how the eyes detect motion.  The team  showed that pairs of neurons positioned along a given direction together cause a third neuron to fire in response to images moving in the same direction. People can only make sense of visual information once it has been interpreted by the brain, but some of this info is processed partly by neurons in the retina. When light enters the eye, it is captured by photoreceptor cells, which convert the light into electrical impulses & transmit them to deeper layers of the retina. 
J Kim & team MIT now can describe what actually happens – Photoreceptors relay their signals via ‘bipolar neurons’, named this way because they have two stems that jut out of the cell's body in opposite directions. The signal then transits through ‘starburst amacrine cells’- which have filaments, or dendrites, that extend in all directions similarly to light rays out of a star - before reaching the cells that form the optic nerve, which relays them into the brain.
The team analysed high-resolution electron microscope images of a mouse retina with the help of nearly 2,200 members of EyeWire , an online ‘citizen-science’ game set up to help with brain-mapping efforts. Players traced the pathways through the layers of cells to create a high-resolution wiring diagram of part of the retina. 

Excerpts from September 2016  Research Updates 

AMD-Retina Research Update:

Perspectives on reticular pseudodrusen in age-related macular degeneration (AMD): Drusen have been considered the clinical hallmark of AMD  Reticular pseudodrusen (RPD), although  described about 25 years ago, have only been recently recognized as an additional clinical phenotype* of AMD with distinct characteristics on multimodal imaging and significant impact on visual function. Eyes with RPD are at greater risk of progression to advanced AMD compared with eyes with drusen only. RPD can also occur in the absence of drusen.  Evidence suggests that RPD are associated with changes inside the RPE. Therefore, new avenues regarding the development of AMD are highlighted by these recent observations. * Phenotype - physical appearance of an organism as distinguished from its genetic makeup. The phenotype of an organism depends on which genes are dominant and on the interaction between genes and environment.] Survey of Ophthalmology Sep-Oct 2016
%% Pathophysiological Differences in Early age-related macular degeneration (AMD) May Point to New Therapeutic Targets:  "We found a different response in reticular pseudodrusen compared to medium/ large drusen, suggesting a different pathophysiology," (change in function due to disease) said senior author Dr. G Querques  University of Paris. "These results may give us the opportunity to identify further therapeutic targets in this phenotype of early AMD,"   The team investigated the response to carotenoid supplementation in this study by measuring macular pigment optical density (MPOD) and retinal sensitivity.  There were  20 patients with only medium/ large drusen, 19 with only reticular pseudodrusen (RPD) and 15 age- and sex-matched controls.  After 3 months of vitamin supplements (lutein 10 mg/day and zeaxanthin 2 mg/day), the mean MPOD increased significantly in patients with RPD, with no significant changes in mean retinal sensitivity and best-corrected visual acuity (BCVA). Medium/large drusen changes on MPOD, retinal sensitivity and BCVA were not significant.  Dr. J Loewenstein, Harvard Medical School commented "As the authors state, dietary carotenoids are selectively transported to the macula, so one would expect that nutritional supplementation with carotenoids could increase their concentration in the macula," .."Previous cross-sectional studies of diet and AMD have suggested that individuals with higher consumption of foods containing carotenoids have lower risk of AMD. Also, a large multicenter randomized trial of nutritional supplements for patients with AMD has suggested that the supplements lower the risk of AMD progression."  Dr. Q said future studies also need to be larger. "If our results are confirmed, the use of carotenoid supplementation should be strongly encouraged according to the phenotype of early AMD. ... we plan to investigate other features of patients with early-stage of AMD."  Source: http://bit.ly/2cTXevj Br J Ophthalmol 2016. Reuters Health Information © 2016 article: L Janeczko Sep 13, 2016 Medscape

Diabetes Research Update:

%% Laser versus Drugs for Diabetic Retinopathy: Mostly a Toss-Up: In patients with proliferative retinopathy, patient-centered outcomes were mostly similar following treatment with ranibizumab (Lucentis) or panretinal photocoagulation (PRP), results of a randomized trial of 216 patients with type 1 or 2 diabetes indicated.  The exceptions: lucentis was associated with reduced loss in work productivity and with better performance in some aspects of driving relative to the laser therapy, according to A Glassman,  Jaeb Center for Health Research. The  subjects had one eye randomized to treatment with the drug or PRP, with outcomes measured with the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and two other questionnaires.  There were no statistically significant differences between the two study groups in the change from baseline to 1 or 2 years.  But, Glassman cautioned, "an important limitation of these Protocol S results is that the questionnaire-based subjective measurements are typically more variable than objective measurements of function.  QD Nguyen, University of Nebraska,said "Protocol S has provided very important information that can guide the management of PDR and that should be discussed carefully with patients. PRP has been the standard of care for PDR during the past 3 decades. According to Protocol S, pharmaco therapy with an anti-VEGF agent such as ranibizumab may provide similar benefits and may have advantages in certain parameters, such as driving-related outcomes. With anti-VEGF therapy, there are also benefits of not having a destructive procedure, but such benefits must be balanced with the cost and the frequency of treatments and office visits associated with pharmacotherapy."  Funded mainly by the NEI and Institute of Diabetes and Digestive and Kidney Diseases. Genentech provided ranibizumab and funding to defray clinical site costs. Glassman disclosed funding from Regeneron, and Genentech. Nguyen disclosed funding from includes AbbVie, and XOMA.  Source Ref: Beaulieu WT, et al  Am J Ophthalmol 2016;MedPage Today 9/8/2016

%% EASD: Benefits of T2D Triple Therapy Hold Up Over Time:  Treating newly diagnosed diabetes patients upfront with metformin/ pioglitazone (Actos)/ exenatide (Byetta) therapy appeared to lower blood glucose and reduce hypoglycemic (hypo) events better than standard sequential therapy.   After 36 months of treatment, patients who were treated with the combination had a HbA1c of 5.8% vs 6.71% if they were treated with metformin, had a sulfonylurea added on and, then had basal insulin added, said M Abdul-Ghani,University of Texas, and team. . He said that hypo events occurred in 2% of the patients on conventional sequential therapy and in 0.25% of patients who were started on triple therapy.  There were 165 total patients in the study. Triple therapy consisted of metformin, at 1,000/mg a day for 1 month, and then 2,000 mg a day for the remainder of the trial; pioglitazone (actos) at 15 mg a day titrated to 30 mg a day; and exenatide (byetta,) injected in doses of 5 µg a day and titrated to 10 µg a day.  89 of the patients were treated sequentially --during 1 month, metformin was increased to a dose of 200 mg a day and glipizide (Glucotrol) at 5 mg a day was added in response to fasting glucose levels. Three-fourths of patients in the triple therapy group achieved and stayed within their HbA1c goal of 6.5% versus around 55% of those on conventional therapy. Patients on triple therapy lost about 3 kg (about 6.6 lbs) over the course of the 3 years of treatment, vs 3.7 kg weight gain among those on conventional therapy.  "The take-home message: Treat the disease -- diabetes, not its symptom -hyperglycemia. Treat the patient, not his blood sugar," Abdul-Ghani stated.  G Bernstein, MD, endocrinologist at Lenox Hill Hospital said that "it is becoming clear that combination therapy for type 2 diabetes is now a basic principle of treatment. This [triple therapy] takes advantage of the different mechanisms of action of each drug," Dr. B who was not involved in the study added, "For example, the 3 drugs block glucose production in the liver, enhance the responsiveness to glucose in the Beta cell, and increase insulin sensitivity. The platform upon which other drugs are used is metformin but that platform is being expanded to add GLP-1 agonists and build upon that basic combination... What the study doesn't do is compare triple versus sequential therapy using the same drugs. The future is about more combinations and development of longer acting medications." Supported by American Diabetes Association.  Abdul-Ghani and Bernstein disclosed no relevant relationships with industry.  Source Ref: DeFronzo R, et al EASD 2016. MedPage Today 9.14.2016

Glaucoma  Research Update:

%% Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys:  Preclinical efficacy study in a crossover design in female monkeys with induced glaucoma in 1 eye.    Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the a hydrogel lathed into a contact lens. For both contact lenses the IOP was statistically significantly reduced versus the untreated baseline at most time points measured. CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 and at several time points on day 8. Conclusions - Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.  Partly presented at: Glaucoma 360: New Horizons Forum, Jan 2016,and the Association for Research in Vision and Ophthalmology Annual Meeting, May  2016. Joseph B. Ciolino, MD Ophthalmology 123 October 2016
%% From- The Dark Side of Medication - Many systemic and topical drugs can cause or worsen dry eye disease (DED).  DED is a common ophthalmic disorder that affects a predominantly older population and is diagnosed in women twice as often as in men.  In some patients, DED symptoms are exacerbated by medications that interfere with proper tear production or induce allergic or inflammatory responses in eyes. The sensitivity of DED patients to different medications varies, and clinicians must be aware of all prescribed and over-the-counter drugs in use in order to diagnose a causative agent.    AT A GLANCE - Preservatives in multiuse eye drop bottles such as benzalkonium chloride (BAK) are toxic to the ocular surface. Some medications now use gentler oxidative-type preservatives that cause less ocular surface damage and discomfort. Other eye drops are available in preservative-free  formulas.  Systemic medications are implicated in the aggravation of DED including b-blockers, ACE inhibitors, and diuretics. Antihistamines and antidepressants, also cause adverse effects.         Glaucoma medications, while generally well tolerated, induce adverse effects that may be exacerbated in DED patients. Some of these effects may be due to the presence of BAK, but each class of glaucoma medication also contributes to DED symptoms directly.  Prostaglandins (PGAs) and prostamides reduce IOP by increasing the outflow of aqueous humor produced by the front chamber of the eye, and these agents are often the first line of glaucoma treatment. PGA use increases chalazion* formation and subsequent abnormalities in the tear film and induces conjunctival inflammation. [*blocked eyelid cysts (meibomian gland].  b -BLOCKERS reduce aqueous humor production. Many b-blocker formulations contain BAK, which accounts for some of the reported discomfort. However, nonpreserved b-blockers cause more ocular surface damage than PGAs and brimonidine, indicating that the active ingredient promotes DED symptoms directly.   The a-agonist brimonidine lowers IOP through decrease of aqueous humor production plus increase in outflow.  Allergic conjunctivitis and anterior uveitis often occur following long-term use of 0.2% brimonidine drops, which are preserved with BAK.  Recently, formulas using 0.15% and 0.1% brimonidine and the preservative Purite have been shown to lower IOP as effectively as 0.2% brimonidine, but with a reduction in ocular allergy of at least 41%.  The carbonic anhydrase inhibitors dorzolamide  (Trusopt) and brinzolamide (Azopt) reduce aqueous production and are often used in combination with other glaucoma medications. Burning or stinging during instillation are common adverse effects of dorzolamide, likely because of its low pH of 5.6. Less discomfort is reported with brinzolamide, which has a pH of 7.5, close to that of tears.  Timolol, dorzolamide/ timolol fixed combination, latanoprost, and tafluprost, as well as numerous over-the-counter artificial tears, are now available in preservative-free formulations. When feasible, these medications may be the best choices for DED patients.   Second-tier alternatives are medicines containing milder, non-BAK preservatives, followed by BAK-containing options.   Sarah Marshall, PhD Sacred Heart University, financial interest: none acknowledged; Robert Noecker, MD, MBAf, Yale School of Medicine, Glaucoma Today July-August 2016
Dawn Wilcox BSN RN, Editor, Coordinator  The Health Library  Vista Center    9/27/2016


%% 10/14 Potential Topical Treatment for Macular Degeneration  New study reports successful use in mice; implications for both forms of AMD.The findings, are the first to report successful topical use of a compound capable of inhibiting symptoms assoc with both dry AMD (the earlier form) & wet AMD (the rarer, later form) & could represent a breakthrough for treatment of these conditions.
  AMD is among the leading causes of blindness among the elderly. Currently, there is no treatment for dry AMD, & wet AMD can only be treated with regular injections into the eye.
The Tufts’ team, led by R Kumar-Singh, reported in their “proof of concept” study that topical application [eye drops] of pyridoxal phosphate-6 -azophenyl-2',4'-disulfonic acid, a compound called PPADS, inhibits damage to the tissues in the eye that impacts the individual’s ability to see color & fine detail, as well as reduces the growth of extraneous blood vessels in the back of the eye related to advanced AMD. According to NEI more than 7 mil pts in the US are at  risk of developing AMD.  Factors that contribute to the development of AMD include age, diet, smoking, & genetic predisposition. Dry AMD is the more common/less serious stage of AMD, characterized by the slow loss or blurring of central vision in spots. Wet AMD, which almost always begins as dry AMD occurs in approx 10% of AMD pts, is more advanced & characterized by the development of blood vessels in the back of the eye that often leak and damage the surrounding tissues. Only the wet form of AMD can be treated, with an ophthalmologist administering injections every 4-12 wks that can be uncomfortable, risky, & burdensome to pts. From Bright Focus-
 new name for Amer Health Assist Found

Sleep Apnea:
%% 10/28 Emerging Technologies Look Deeper Into the Eyes to Catch Signs of Disease:  - If you've ever been sleep-deprived, you've probably had a firsthand glimpse of the blood vessels in your eyes. But what you haven't seen & what many eye care professionals cannot see as well as they would like, are the vessels closest to the retina, the light-sensitive tissue at the back of the eye.  The National Eye Institute,[NEI] part of the Nat Instit of Health, [NIH] is helping researchers develop new retinal imaging methods to solve this problem. Such methods have the potential to improve diagnosis and treatment of common eye diseases like AMD & diabetic retinopathy. These diseases can cause a variety of defects in blood vessels inside the eye, including vessel loss, the growth of abnormal vessels, and small bulges that can rupture (called aneurysms). "It makes sense to diagnose and monitor these conditions as closely as possible so that we can provide timely treatment," said A Dubra "The main goal is to avoid irreversible damage," Since the 1960s, the gold standard test for viewing abnormal blood vessels in the eye has been fluorescein angiography [FA] If an eye care professional detects signs of blood vessel abnormalities during a comprehensive dilated eye exam, this test is often the next step. Fluorescein is a dye that glows green under fluorescent light. The dye is typically injected into an arm vein. A camera is then used to take pictures as the dye moves through bloodstream into the eye, making it possible to see abnormal or damaged vessels. Clinicians & researchers are especially interested in seeing blood vessels nearest the retina, because those vessels may show early signs of distress in some diseases. But conventional FA isn't powerful enough to see small retinal vessels and capillaries in fine detail. Adaptive optics (AO) is one technology helping to overcome this problem. It deals with the tendency of light to become distorted as it passes through different media such as air, water, or living tissue. AO was originally developed because astronomers
wanted to get a clear view of objects in space, without distortions caused by the atmosphere. Buteye care experts have a similar problem: When light is shined into the eye, it is distorted by the cornea (the front, transparent part of the eye) & the lens. AO systems typically use a sensor to measure the pattern of blurring & a flexible mirror to correct it.  Dubra collaborated with R Rosen,NY Eye and Ear Infirmary to build a device incorporating AO with FA. In a recent NEI study of 10 healthy volunteers, they found that the combined tech enabled them to see capillaries, tiny aneurysms, & other fine details of retinal blood vessels that aren't visible by standard fluorescein angiography. Researchers are also working to enhance another method. OCT which has only been around since the early 1990s. It's similar to ultrasound, which creates images of living tissues by bouncing sound waves off of them. The difference is that OCT uses light waves instead. A painless infrared beam is scanned across the eye multiple times, creating virtual slices that are each less than one-tenth the thickness of a human hair. These slices makes it possible to view the retina and other tissues in cross-section rather than face-on.  J S Werner,UC Davis, is working on combining AO with OCT. He's also developed a new version of OCT called phase- variance [PV] OCT. "With PV OCT, instead of acquiring each slice once, we acquire every slice 3 times in a row, and then we align them and ask what's different," Werner & team used PV OCT to examine the eyes of 2 pts  in their 60s. One had no history of eye disease and the other had a type of advanced AMD called geographic atrophy. The researchers were able to see retinal vessels, as well as small vessels in a layer of tissue underneath the retina called the choriocapillaris. In the person with AMD, they detected a loss of these small choroidal vessels, which typically aren't visible with fluorescein angiography or other standard methods. 
Looking ahead - It may be a few years before phase-variance OCT and AO-enhanced imaging reaches your eye care professional's office. But experts say that these technologies will quickly expand into more research settings & clinical trials, where they may enable more efficient testing of new treatments. "For AMD & other eye diseases, these techs have the potential to resolve small changes in the eye that occur as vision slowly deteriorates. That could help investigators monitor clinical trial pts more closely and detect the effects of new drugs much faster," said Matthew McMahon, NEI.
From ScienceDaily

Glaucoma:

9/27/16 Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys:  Preclinical efficacy study in a crossover design in female monkeys with induced glaucoma in 1 eye.    Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the a hydrogel lathed into a contact lens. For both contact lenses the IOP was statistically significantly reduced versus the untreated baseline at most time points measured. CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 and at several time points on day 8. Conclusions - Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.  Partly presented at: Glaucoma 360: New Horizons Forum, Jan 2016,and the Association for Research in Vision and Ophthalmology Annual Meeting, May  2016. Joseph B. Ciolino, MD Ophthalmology 123 October 2016
%% From- The Dark Side of Medication - Many systemic and topical drugs can cause or worsen dry eye disease (DED).  DED is a common ophthalmic disorder that affects a predominantly older population and is diagnosed in women twice as often as in men.  In some patients, DED symptoms are exacerbated by medications that interfere with proper tear production or induce allergic or inflammatory responses in eyes. The sensitivity of DED patients to different medications varies, and clinicians must be aware of all prescribed and over-the-counter drugs in use in order to diagnose a causative agent.    AT A GLANCE - Preservatives in multiuse eye drop bottles such as benzalkonium chloride (BAK) are toxic to the ocular surface. Some medications now use gentler oxidative-type preservatives that cause less ocular surface damage and discomfort. Other eye drops are available in preservative-free  formulas.  Systemic medications are implicated in the aggravation of DED including b-blockers, ACE inhibitors, and diuretics. Antihistamines and antidepressants, also cause adverse effects.         Glaucoma medications, while generally well tolerated, induce adverse effects that may be exacerbated in DED patients. Some of these effects may be due to the presence of BAK, but each class of glaucoma medication also contributes to DED symptoms directly.  Prostaglandins (PGAs) and prostamides reduce IOP by increasing the outflow of aqueous humor produced by the front chamber of the eye, and these agents are often the first line of glaucoma treatment. PGA use increases chalazion* formation and subsequent abnormalities in the tear film and induces conjunctival inflammation. [*blocked eyelid cysts (meibomian gland].  b -BLOCKERS reduce aqueous humor production. Many b-blocker formulations contain BAK, which accounts for some of the reported discomfort. However, nonpreserved b-blockers cause more ocular surface damage than PGAs and brimonidine, indicating that the active ingredient promotes DED symptoms directly.   The a-agonist brimonidine lowers IOP through decrease of aqueous humor production plus increase in outflow.  Allergic conjunctivitis and anterior uveitis often occur following long-term use of 0.2% brimonidine drops, which are preserved with BAK.  Recently, formulas using 0.15% and 0.1% brimonidine and the preservative Purite have been shown to lower IOP as effectively as 0.2% brimonidine, but with a reduction in ocular allergy of at least 41%.  The carbonic anhydrase inhibitors dorzolamide  (Trusopt) and brinzolamide (Azopt) reduce aqueous production and are often used in combination with other glaucoma medications. Burning or stinging during instillation are common adverse effects of dorzolamide, likely because of its low pH of 5.6. Less discomfort is reported with brinzolamide, which has a pH of 7.5, close to that of tears.  Timolol, dorzolamide/ timolol fixed combination, latanoprost, and tafluprost, as well as numerous over-the-counter artificial tears, are now available in preservative-free formulations. When feasible, these medications may be the best choices for DED patients.   Second-tier alternatives are medicines containing milder, non-BAK preservatives, followed by BAK-containing options.   Sarah Marshall, PhD Sacred Heart University, financial interest: none acknowledged; Robert Noecker, MD, MBAf, Yale School of Medicine, Glaucoma Today July-August 2016


GRF Glaucoma Diagnosis & Treatment a Preview of the Future:   notes from lecture by Jeffrey Golberg, MD,PhD Oct 1,2013
Glaucoma is progressive optic neuropathy [ON]. ON fibers do not normally regenerate when lost. These is a typical pattern of loss of the retinal ganglion cells [RGC] starting with those responsible for peripheral vision. Glaucoma is the world’s leading cause of irreversible blindness. The cause is as yet unknown but IOP level &  increasing age are associated.  In order to diagnose glaucoma now, the optic nerve must be visualized.
Diagnosis - Current problems, questions  how do we measure the disfunction, difference between injured fiber & totally dysfunctional/ dead cells.  How can we detect progression & signs of risk of progression. We have no markers now to determine when a drug (perhaps a growth factor) RX is needed to protect cells; it takes too long to measure effect or lack of effect of a treatment.  Recent findings of the Catalyst for a cure consortium determined that  injured mamalian cells are less electrically active than normal ones. If the cell is intentionally damaged in the lab, reduction of it’s electrical activity is found within 16 hrs.  There are also changes in the shapes of cells after axon is injured as well as reduced oxygen levels.  So the scientists will want to measure blood flow in the retina.  New imaging techniques now shows injured cells.  At the present time, only the measurement of IOP & visual field tests are available & these can take years to show progression- the teams want to identify G progression sooner so treatment can be started.
—Treatment - how can we fix the optic nerve in glaucoma to restore lost vision.   Researchers have found some of the genes involved in regeneration of nerve cells such as KLF9. Viral vectors are being used to deliver specific genes. In humans with Lebers Congenital Amaurosis, a form of RP due to a single gene, this technique has been used sucessfully in on going trials. In lab studies imaging shows axon fibers regrowing in the right direction.  
2. Electrical stimulation to RGC in lab culture has resulted in increased cell survival. Using a contact lens outside the eye to stimulate RGC in animals is being tried also with increased cell survival.  At birth humans have 1 million RGC; with G the number drops.
3. Stem cells grown from the pts own cells are called auto stem cells. Implanting these stem cells around surviving RGCs will help them survive.
4.Work is being done on using magnetic nano-particles to pull regrowing axons in the right direction. These nano- particles are so much smaller than cells that they don’t affect the body’s kidneys etc.  Dr. Goldberg and his team have been running a clinical trial for the past 1½ yrs in the effort to find a new treatment not only to preserve but enhance vision affected by glaucoma.  In a 20min surgery they inserted a 1x3mm inplant filled with CNTP. The device  pumps out the drug. The 22 pts have had no adverse effects.  The trial results are due to be announced in Feb 2014  GRF Daniel Scott Weston G ch Research Lecture, 10/1/13 dw for thl
%% DRL   NIH 10/21 Large study to examine if vitamin D prevents diabetes:    The Vit D & T2DM (D2d) study will  include about 2,500pts  Its goal is to learn if vit D - specifically D3 (cholecalciferol) - will prevent or delay T2 in adults age 30 or older with pre-DM. Pts w pre-DM have blood glucose levels that  are higher than normal but not high enough to be called diabetes. Vit D use has risen sharply in  the US in the last 15 years, since it has been suggested as a remedy for a  variety of conditions, including prevention of T2. But we need rigorous  testing to determine if vit D will help prevent DM. That’s what D2d  will do... until this large, randomized-controlled clinical trial [RCT] is complete, we won’t know if taking vit D supplements lowers the risk of DM, said A G Pittas, lead investigator.  D2d is the first study to directly examine if a daily dose  of 4,000 International
Units (IUs) - greater than a typical adult  intake of 600-800 IUs a day,  helps keep pts with pre-DM from  getting T2DM. Based on previous  studies, the team speculates that vit D could reduce the diabetes risk by 25%. Half of the participants will receive vitamin D. The other half will receive a  placebo - a pill that has no drug effect. Subjects  s will have check-ups for the study twice a year, & will receive regular health care through their own  health care providers. The study will continue until enough people have developed T2 to be able to make
a scientifically valid comparison between DM development in the two groups, likely about four years.

Diabetes Research List     AUGUST  - 2013    

Diabetes Research Contents:

 1. Low Blood Sugar Levels May Pose Heart Risks for Diabetics
 2. Hypoglycemia Happens at All HbA1c Levels
 3. Device Aids Calculation of Insulin Bolus:    
 4.Abbreviations

 
1.%% MP 7/31 Low Blood Sugar Levels May Pose Heart Risks for Diabetics..:   T2DM pts with dangerously low blood sugar levels may be at increased risk for cardiovascular disease. Given their findings, "less stringent glycemic targets may be considered for T2 pts at high risk of hypoglycemia (severely low BS)," the researchers said.  They analyzed findings of 6 studies [903,000pts;5yr]0.6% to 5.8% of patients developed severe hypo.  The results suggest that severe hypoglycemia is associated with a two-fold increased risk of CVD. Because of this, preventing severe hypo in people with T2 may be important to prevent cardiovascular disease. The link between severe hypoglycemia and increased cardiovascular disease risk has
previously been explained by pts having one or more other serious illnesses, but this is an unlikely explanation, the team said. They said the incidence of serious illnesses would need to be "unrealistically high" among patients who developed severe hypoglycemia, and the link between serious illnesses & CVD would have to be "extremely strong."  BMJ.com , news release, July 30, 2013

2.%% MPD 7/31  Hypoglycemia Happens at All HbA1c Levels:
Compared to a baseline HbA1c of 7-7.9%, no level of HbA1c from less than 6% to 9% or higher, had a significantly different relative risk of hypoglycemia in a model fully adjusted for age, DM duration, & category of DM medication. [9094 T2pts]K Lipska & team  assessed incidence of DM complications, including severe hypogly cemia, & sociodemographic factors. These data were linked with clinical, pharmacy,& lab data from pts’ electronic medical records. Pts with DM for more than 10 yrs were significantly more likely to report severe hypo than those with a shorter duration(13.9 vs 8.3%) there was no sig relationship between HbA1c & age,or category of DM medication. The adjusted relative risk showed there was no sig difference between level of HbA1c for risk of severe hypo."Contrary to conventional wisdom, hypoglycemia occurs just as frequently among those with poor glycemic control as it does in those achieving near-normal glycemia," they concluded. support Nat Inst on Aging & Nat Heart, Lung and Blood Institute.


3.%% MPD 8/1  Device Aids Calculation of Insulin Bolus:    This was a prospective, randomized study [218 pts;av A1C 8.9%;26wk]  predom inantly T1, evaluated the use of an automated bolus adviser to calculate insulin dosages compared with manual bolus calculation.  R Ziegler & team report On average, pts using the glucose meter with the automated bolus adviser had a drop in A1C from baseline of 0.7%. That compared with a reduction of 0.5% for those doing the calculation by hand.   However,56% of those using the automated system reached the study goal of more than a 0.5% reduction in A1C, compared with 34.4% of those calculating by hand.  supported by Roche Diagnostics

4.%%


%% Abbreviations-acronyms fup-follow up;pt- patient/ participant ; DM - diabetes Mellitus; T1- type 1 DM; T2 - type 2; DME - diabetic macular edema;DR - DM retinopathy; BCVA - best corrected visual acuity;BMI -  body mass index; BS/BG- blood sugar/ glucose; ETDR- Early RX DM Retinopathy Study Chart; HA1C, glycated hemoglobin A1C; BP -blood pressure; CVD-cardiovascular disease; OCT-optical coherence tomography; RCT -Randomized controlled trial; VA-visual acuity.  ADA - Am Diab Ass;M- Medscape;MP- Medline Plus; MPD - Med Page Today;MXP- Med Express NEI - Nat Eye Institute; SciA-Scientific Amer.   Definitions via online Medical dictionaries.  Disclaimer, I am a BSN RN but not a diabetic or DM educator. Assistant Editor: Cam Acker, 50yr T1DM survivor. Reports  excerpted unless otherwise noted. [translations/explanations by thl] This project is done as a courtesy to the blind/visually impaired & diabetic communities. Dawn Wilcox BSN RN Coordinator The Health Library at Vista Center; an affiliate of the Stanford Hospital Health Library.   contact above e-mail or thl@vistacenter.org

AMD - Retina Research List    July 2013

Retinal Research Contents:

 1. Los Alamos team makes contributions to first bionic eye
 2. Ozurdex for RX  macular edema assoc with retinal vein occlusion
 3. [infection]Outbreak after Intravitreal [avastin] 1Year Outcome
 4. Darker Not Better for Sunglasses
 5. Surgical Management of Rhegmatogenous Retinal Detachment
 6. Genes Could  Hold the Key to AMD
 7. .complete description of gene expression in human retina
 8.  Avastin as Good as Lucentis for AMD  
 9.  Ciliary Neurotrophic Factor - Intra ocular Implants trail RP
10. Influence of Cataract Surgery-physiology Measurements RP
11. Recycling in the eye promotes good vision
12. Stem cell retina RX might provide ..'cure' for blindness   UK
13. Bionic contact lenses turn touch into vision              Isreal
14. Engineered virus designed to restore sight               UC Berkeley

1.%% MXP 7/13 Lab team makes unique contributions to the first bionic eye

As part of the multi-institutional Artificial Retina Project, Los Alamos researchers helped develop the first bionic eye. Argus II will help people blinded by the rare hereditary disease RP or seniors suffering from severe AMD. Argus II operates by using a miniature camera mounted in eyeglasses that captures images & wirelessly sends the info to a microprocessor (worn on a belt) that converts the data to an electronic signal. Pulses from an electrode array against the pt’s retina in the back of the eye stimulate the optic nerve &, ultimately, the brain, which perceives patterns of light correspond ing to the stimulated electrodes. Blind pts can learn to interpret these visual patterns .  The Los Alamos team developed better ways to visualize & interpret the resulting neural activity patterns. The team also advised the consortium on the use of technologies to map the human brain function stimulated by the devices or by normal biological vision. The DOE Artificial Retina Project is a multi-institu tional collaborative effort..The 10-year project involved labs [includes] Lawrence Livermore, Los Alamos, Doheny Eye USC, U Utah, UCSB.

2.%%  Eye 27 Jul 2013   12-month experience with Ozurdex for the treatment of macular edema associated with retinal vein occlusion

[RVO] Purpose -evaluate the efficacy/ safety of a [steroid] implant (Ozurdex) alone or in combination with bevacizumab [avastin] [64eyes;12m] Conclusion - Combined treatment showed slightly better functional outcome for CRVO pts. Increased intraocular pressure & cataract progression was frequent & should be considered when an individual treatment is planned.

3. %% Oph 120 July2013  Endophthalmitis [infection] Outbreak after Intravitreal Injection of Bevacizumab [avastin]:

One-Year Outcomes
Results 12 eyes of 12pts who developed endophthalmitis after receiving intravit bevacizumab prepared by a single compounding pharmacy. For treatmen 8 pts (67%) underwent pars plana vitrectomy (PPV) [removal of vitreous at back of eye]. After 12m follow-up, outcomes have been poor. 7 pts required [removal of eye] only 1 patient regained pre- injection visual acuity. Molecular testing confirmed the presence of Streptococcus mitis/oralis in vitreous specimens & 7 unused syringes prepared by the [above] pharmacy. FDA investigation noted deviations from standard sterile technique, inconsistent documentation, & inadequate testing of equipment required for safe preparation of medications. Conclusions In this outbreak outcomes have been generally poor, & PPV did not improve visual results at 1-year follow-up.

4.%% MP 7/7  Sun Damage: Darker Not Better for Sunglasses

Seeking some new shades? There is a whole lot more than style at stake, experts say. "Most people think the darker, the better," E Kondrot, Oph. Said "But that's not the case."     Darker shades that don't protect against the sun's ultraviolet (UV) light actually allow more of these higher-energy waves into the eye, since the pupils dilate in the low-light conditions created by the heavily tinted lenses - potentially leading to greater damage. Dark shades cause more harm because you lose that protective reaction: you don't squint, your pupils don't constrict. And you get excessive amounts of sunlight into the eyes."  The key, experts say, is to choose a pair that guarantees to shut out UVA & UVB rays. The wave lengths of visible light are squeezed into a small spot on the electromagnetic spectrum, ranging from about 400nm (nanometers) to 700 nm- in terms of color, that's from violet to red. Beyond red wavelengths are longer &  lower- energy waves, like infrared & radio waves; but beyond violet light are shorter wavelengths that eventually turn into the ionizing radiation of X-rays & gamma rays.  In between these DNA-damaging wavelengths and visible light is ultraviolet, generally  in the range of 100 nm to 400 nm. .. Even though the UVA & UVB that makes it to the earth's surface isn't ionizing, it can still alter chemical bonds in molecules- as evidenced by sunburn. Like the skin, the eye also absorbs UV, with shorter wavelengths- the more dangerous ones-being caught by the cornea, & longer wavelengths potentially reaching the lens & retina.That's why ophthalmologists urge that UVA/UVB protection is more important in sunglasses than the extent of the tint. "You should look for labels that say UV absorption 99 -100%," M Moshirfar, U Utah, said. "You may also see a label that says UV absorption up to 400nm. That also means the absorption is up to 100% of UV." He added that polarized lenses don't do anything to stop UV light from hitting the eye; [but] they help to cut down on glare.
Recent work has shown that AMD may have more to do with blue wavelengths in visible light than with UV light. In a recent review in May issue of the journal International Oph. Yam & team concluded that there's "insufficient evidence to determine whether AMD is related to UV exposure.The lack of a clear association between UV exposure & AMD is not surprising, because the lens absorbs almost all UVB & only very small amounts of this waveband can reach the retina, Blue light has been shown to be on the portion of the visible spectrum that produces the most photochemical damage to animal retinal pigment epithelium cells."

5.%% Oph120 Jul 2013  Surgical Management of Rhegmatogenous Retinal Detachment (RRD):

A Meta-Analysis of Randomized Controlled Trials  Purpose - To examine possible differences in clinical outcomes between pars plana vitrectomy (PPV) and scleral buckling (SB) for uncomplicated RRD.  7 studies PPV (636 eyes) ; SB (670 eyes)Conclusions: There were no significant differences in the proportions of primary reattachment in the PPV & SB groups in phakic [has natural lens] eyes. The SB-treated phakic eyes had better postop BCVA at 6months or more. This is most likely related to higher rates of cataract progression in PPV-treated phakic eyes. There were no significant differences in proportions of primary reattachment & postop BCVA at 6m or more in pseudophakic/ aphakic eyes. [artificial or no lens]

6.%% JH July 2013 Genes Could  Hold the Key to AMD 

It's been known for some time that heredity is a major risk factor for (AMD), which afflicts nearly 7% of pts over age 40. Thanks to the results of a new study into the molecular underpinnings of AMD, the medical field is closer to being able to identify people  whose gene sets could put them at increased risk for this leading cause of vision loss. The study was published in Genome Medicine Vol 4. The study analyzed ocular tissue from 68 human donor eyes, including 26 with AMD, 11 with signs of potential AMD & 31 disease free controls. The team uncovered more than 50 genes that are overexpressed in AMD. They then narrowed the field to 20 genes that they believe are predictive of a clinical age-related macular degeneration diagnosis. These include genes in layers of blood vessels & tissue behind the retina affected by AMD - genes associated with cell-based inflammatory responses - & genes within the retina that are part of the body's immune system. Takeaway. The findings could offer new targets for the development of AMD diagnosis & therapies. Because the study identifies immune responsiveness as a crucial factor, the findings also suggest that [medications] targeting core immunological processes could potentially offer effective AMD RX.

7.%% MXP 7/18   Researchers report a complete description of gene expression in the human retina   

A team -Mass Eye & Ear & Harvard have published the most thorough description of gene expression in the human retina in the journal BMC Genomics.  The retina is the neural tissue in the back of the eye that initiates vision. It is respons ible to receiving light signals, converting them into neurologic signals & sending them to the brain so that we can see. If one thinks of the eye as a camera, the retina in the "film". The team used a technique called RNA sequencing to identify all of the messenger RNAs (mRNAs) produced in the human retina. The resulting catalog demonstrates that the majority of the 20,000+ genes in the human body are expressed in the retina. Dr. Farkas & team found almost 30,000 novel [new] exons & over 100 potential genes that had not been identified previously. Exons are the portions of the genome that are used to encode proteins or other genetic elements. Several thousand of these exons appear to be used specifically in the retina. ..This work is valuable to help scientists understand how the retina works, & how it is affected by disease.  Dr Pierce & team study inherited retinal degenerations, which are common causes of vision loss. These diseases are caused by misspellings or mutations in genes that are needed for vision. To date, scientists have identified more than 200 retinal degeneration disease genes, but still can't find the cause of disease for up to ½ of the pts affected by these disorders. Identifying the genetic cause of pts retinal degeneration has become especially important with the recent success of clinical trials of gene therapy for RPE65 Leber congenital amaurosis (LCA). As a follow-up to these initial proof-of- concept trials, clinical trials of gene therapy for 4 other genetic forms of inherited retinal degener ation are currently in progress.

8.%%MPD 7/18 Avastin as Good as Lucentis for AMD  

Chakravarthy & team reported the final analysis of the CATT & IVAN data. 610pts 50yrs+ who had active, untreated [wet AMD] & a BCVA of at least 25 letters read on a standard vision chart were randomized to intravit injections of [either drug] in either a continuous monthly regimen or a prn regimen. At 2 yrs there was no difference between the drugs for any of efficacy outcomes. [effectiveness] Continuous & prn RX yielded similar results for BCVA although continuous adm was superior for near visual acuity & contrast sensitivity. New geographic atrophy was significantly more common with continuous adm, however (34 vs 26%).  "The comparisons between the drugs after 2 yrs are reassuring, with no suggestion of any difference in mortality or arterial thrombotic [clot] events, which have previously been suggested to be related to use of anti-VEGF drugs," the team wrote. The ideal choice of agent & frequency of administration, however, remains unclear. "Bevacizumab & ranibizumab [avastin lucentis] have similar efficacy & can be considered equivalent in this respect in the RX of neovascular [wet] AMD,"  funded by NIH

9.%% Am J Oph 9 Aug 2013 Randomized Trial of Ciliary Neurotrophic Factor (CNTF)Delivered by Encapsulated Cell Intra ocular Implants for Retinitis Pigmentosa [RP]  [65 late stage; 68 early stage pts])

Pts were randomly assigned to receive a high- or low- dose implant in 1 eye & sham surgery in the fellow eye. Results There were no serious adverse events  Conclusions Long-term intraocular delivery of CNTF is achieved by the encapsulated cell implant. Neither study showed therapeutic benefit.

10.%% Am J Oph 9 Aug 2013 Influence of Cataract Surgery on OCT & Neurophysiology Measurements in Patients  With RP

Purpose To evaluate the effect of uncomplicated cataract phacoemulsification [phaco] on measurements of visual evoked potentials (VEP), pattern electroretinogram (PERG), & macular & retinal nerve fiber layer (RNFL) [35 eyes/35 pts] Conclusions - The presence of cataracts affects VEP amplitude, RNFL, & macular measurements performed with OCT in eyes with RP. Image repeatability significantly improves after cataract  phaco.

11.%% MXP 7/19 Recycling in the eye promotes good vision

Recycling cellular debris within the eye is required for maintaining good vision.  Photo on web page =Inside retinal pigment epithelium [RPE] cells, structures used for recycling engulf and digest spent parts of photoreceptor cells.  Recycling isn't just good for the enviro nment. It's also good for your eyesight.  Researchers have found that good vision depends, at least in part, on a recycling process in the eye that mops up cellular debris & reuses light-sensitive proteins. The findings suggest that disruptions in that process may harm vision & play a key role in the development of eye diseases related to aging, including AMD the leading cause of vision loss in Americans over 50. In the brain, similar defects in the recycling of proteins contribute to other disorders assoc with aging, such as Alzheimer's & Parkinson's.  published online in the journal Cell . "One possibility is that as we age, these recycling pathways can become less efficient and the system becomes clogged," said co-senior author T A Ferguson, "That can cut down on the retina's ability to use vit A, which is crucial to good vision. Working in mice, Ferguson & team showed that vision suffers when the retina can't clear away debris produced by light-sensing photoreceptor cells . The retina is populated with photoreceptors that absorb light & send electrical signals to the brain, allowing us to see. A key component of these photoreceptors is a light-sensitive molecule called rhodopsin. It is rhodopsin that absorbs light, but each rhodopsin molecule only works for a brief stint. Once it has been exposed to light, rhodopsin breaks down and must be recycled to use again. "After rhodopsin absorbs light, it's no good anymore," said Dr. F "But the 'spent' rhodopsin is recharged through a series of chemical reactions so that the whole process can start all over again."  The key player in getting the rhodopsin recharged is a single layer of cells at the back of the retina called the retinal pigment epithelium (RPE), which recycles & recharges a molecule that rhodopsin needs to activate the photoreceptor cells.In addition, the photoreceptor cells them selves also get a little ragged after repeated exposure to light & they, too, are continually shed & renewed each day. The new study found that both the recycling of rhodopsin & clearance of discarded bits of photoreceptors are [started] by a mechanism called autophagy.  "Autophagy is just what it sounds like: self-eating, Under adverse conditions, cells digest their own internal structures. They essentially eat themselves to survive. The process we've studied shares features of autophagy, but also is distinct, and that's very exciting." There is increasing evidence that when operating efficiently, autophagy can help stave off the cellular damage that occurs in age-related diseases such as Alzheimer's. Dr F & team suspect it also may play a role in age-related eye diseases. But autophagy isn't the only mechanism at work in the retina. The retinal pigment epithelium (RPE) also uses a second eating process called phagocytosis to clear away parts of the photoreceptor cells that are constantly shed in the retina. But it turns out that both autophagy - - when cells eat themselves and phagocytosis - when cells eat structures other than themselves -operate through the same pathway. This study of mice showed that  as in people, photore ceptor discs are shed early each morning.. Next, they generated mice whose RPE cells lacked a gene essential for autophagy. " disrupting this unusual form of autophagy also disrupted the process of phagocytosis, The RPE cells weren't able to digest debris from photoreceptors, suggesting that the two mechanisms shared a common pathway in the retina." Using complex techniques to measure vision, the team discovered that although the mice weren't losing photoreceptor cells, they were losing their vision. "Their vision was reduced by 30 -40 %, But when we gave each of the mice a single injection of a molecule to restore the rhodopsin in their photoreceptors, their vision was restored to normal for several days."   The experiments, Ferguson said, suggested that autophagy assists the visual cycle by helping cells recover vit A, which is essential for the recycling of rhodopsin in the photoreceptors. "And that is very interesting because deficiencies in vitamin A are known to lead  to night blindness & other vision problems, We can't really say these mice were 'night blind,' but their vision was reduced because they couldn't efficiently recover enough vit A to restore rhodopsin to the photoreceptors." If that same process were to break down in humans as a function of aging, Dr F believes it could play a role in the vision loss associated with normal aging and with diseases like macular degeneration.  Because previous studies have suggested autophagy can help clear harmful proteins that accumulate in cells during Alzheimer's & Parkinson's disease, new drugs are being developed to boost that recycling process. The team think some of those drugs may be useful in combating age-related vision loss.

12.%% 7/24 Stem cell retina therapy treatment might provide miraculous 'cure' for blindness

Scientists in the UK took stem cells [SC] from mice embryos, put them in a petri dish & coaxed them into becoming photoreceptors, the cells in the retina that catch light. After collecting 200,000 of the SC turned photoreceptors the team then injected the cells into the eyes of blind mice, & some of the cells integrated into the host retina & restored sight. The mice were then run through a maze & examined by optometry to confirm that they did indeed respond to light.  While the work is still years away from helping humans, it is an extremely promising start to curing blindness caused by photoreceptor loss like RP & AMD. The biggest breakthrough that this team was able to achieve was turning the finicky stem cells into stable photoreceptors, instead of deadly cancer cells. "The next step will be to refine this technique using human cells to enable us to start clinical trials." A team in Japan were recently approved to start clinical trials using SC from a pt’s own body.  pub by Britain's Med Research Council & in the journal "Nature Biotechnology."

13.%% 7/23 ISRAEL21c   Bionic contact lenses turn touch into vision, by K Kloosterman   

A new Israeli approach to providing sight to pts with vision impairment uses a technique known as sensory substitution.  Much in the way Braille allows pts who are blind to “see” the written word, a bionic contact lens invented by Prof. Zeev Zalevsky “presses” images onto the surface of the eye to help the brain decipher through touch what the wearer is looking at. The lens, still in a prototype stage, uses electrical signals sent to it from a small transponder, clipped to a pair of glasses or downloaded to a smartphone. A regular off-the-shelf camera, like the one inside a phone, “looks” at a crosswalk, items for sale in the grocery store, or at a loved one’s face, and transmits the encoded image via the lens to the wearer’s cornea. The image gets translated into a tactile sensation that can be interpreted visually. “The cornea has the highest density of tactile sensors in the human body,” the professor says. “There are 600 times more sensors in your cornea than on fingertips which are used to touch & read Braille. And since there are so many tactile sensors in the eyes, one can actually sense & ‘feel’ an image at a very high resolution, helping you really see with your eyes when you are blind,” he says the sensation is similar to feeling a person’s face with one’s hands to understand how they look. “We can do the same by touching projected images from the camera onto the cornea of your eye.”
 If the lens lives up to its promise, it could go way beyond helping pts read. Best of all, it is non-invasive. This approach differs from artificial retinas being developed by companies including Second Sight. Artificial retinas use an impact camera connected with electrodes directly to the visual nerves of the eye. However, the connection holds for just a few years, & those born without a developed visual cortex cannot benefit from this solution. It is also invasive & provides images at very low resolution of only a few pixels, says Dr Z.  Healthy eyes see at a resolution of about one megapixel. The bionic lenses could provide a resolution of tens of thousands of pixels.   This new device still needs to pass clinical trials. But prototypes have been tested on healthy pts. After a few minutes of learning how to associate actual images with the sensations they felt on their fingertips, they could actually “see” using the bionic contact lens.   “After a learning curve, people could recognize a house, a door, a car, even just after a short while wearing this technology,”  The revolutionary product, has more than humanitarian & medical applications. Fitted with an infrared camera, it also has the potential to help law enforcers see in complete darkness.  Zalevsky & the tech-transfer company at the university are hoping for a $1-2 million investment so that a full system and fabrication process could be started. A beta version could be ready within 2 years.  The contact lens would be completely different from the “Google Glass for the blind” being developed by S Shoham using visual sensors in the retina. [AMD-Retina June 2013]  However, both researchers say their solutions can work together.   “The Bar-Ilan U. device concept is what is called sensory substitution- you replace one sense (vision) with another (touch on the cornea). What we’re working on is a retinal prosthesis that tries to artificially activate the original sense of vision. These different approaches are comple mentary.”   Another Israeli invention, OrCam, is an image-process ing/computer vision device that identifies verbally what the wearer is pointing at. Israelis are also developing new tools using sound and joysticks to help the blind see.


14.%% 7/13 Engineered virus designed to restore sight 

UC Berkeley scientists nave  created a ”designer virus” that is able to drive through the white of the eye to the retina at the very back, where it dumps a payload of genetic material that can stop & maybe even reverse, certain types of hereditary blindness.  Their discovery could be a boon for the field of gene therapy [GT] a potential RX for hereditary conditions that involves hijacking a virus & using it to transport healthy DNA to replace defective genetic material. But GT, once widely hailed as a potential cure for so many diseases, has struggled to  produce results. While there have been some small successes in the past decade, notably, among a select group of children with a rare eye disease [LCA] who had  some sight restored after receiving GT, there  have been frequent setbacks too. But a new technique developed at UC Berk. may overcome one of the largest hurdles - precision delivery. The team believes they’ve  harnessed natural evolution & engineered a virus that will go to exactly the right spot in the body, spreading replacement genetic material to the cells that need it.  ”The virus we’ve been using so far for GT, in  limited cases, it’s effective. But  that virus evolved in nature for its own purposes, not our needs,” said D Schaffer. ”It became clear we needed to develop new methods to re-engineer the virus - in effect, to optimize, rather than settle with what nature has given us off the shelf.”  If the technique stands up to experiments in human pts, it could someday be applied to many types of blinding diseases, including conditions like macular degeneration. And it could improve GT for other hereditary conditions  too, from cystic fibrosis ..to Alzheimer’s ..This research, which was detailed in a paper published last month, has only been done in mice & in one macaque, but  the team is optimistic the results will stand up in human pts. The scientists hope to begin  human clinical trials in a  few years.  ”Gene therapy is a very exciting field right now, & their paper is very timely,” said Dr. J Duncan,UCSF oph ”This technique has a lot of promise for expediting GT trials for other diseases & also making trials already under way perhaps more safe & effective.”

Gene therapy involves using a virus’ natural inclination to infect & replicate [copy itself] to deliver replacement to cells with mutations. The idea behind the new technique is to manufacture the best virus possible for delivering that genetic material.  When viruses infect cells, they insert their own genetic material into the DNA of the host cell & take over the cells’ mechanisms to produce more of the virus. But scientists now are able to engineer viruses, essentially removing their DNA & inserting whatever genetic material doctors want to  deliver into the host cell. The problem is that scientists are still at the  mercy of much of the virus’ innate drives. Different viruses target only certain types of cells with a specific protein marker on the  surface - HIV, for example, goes after immune cells, while viruses that cause colds are drawn to cells in the respiratory system.  So in order to get genetic material to the right location in the body,doctors either have to be very precise in where they deliver it - inject the virus into exactly the right spot on the retina, for example - or they have to find a virus that will hone in  on the cells that doctors want to target. But the UCBerk team believe they’ve found an alternative  They used the ideas behind natural evolution to force a virus to evolve into exactly what doctors need. ”We’re sort of mimicking the process that happens with viruses  over millions of years,”  said J Flannery, ”None of the viruses in nature were  doing what we needed  them to do. They were evolved not to give you gene therapy, but to give you the flu or whatever.”   Catalog of Viruses:  Over the past decades, Schaffer has built up a catalog of 2 million  viruses, each slightly different from the rest. To evolve the best virus for getting genetic material into the retina,  where the damage that causes most types of blindness occurs, he screened his catalog to find 10 or so  viruses that would be attracted to cells in that part of the eye.  He then added new mutations to those viruses & again picked out the ones best matched to the task.  Over 9 months, he went through several rounds of this not-so natural natural selection before finally  settling on an engineered virus that seemed to suit their needs.”We threw 100 million  potential solutions at  problem & let evolution select the fittest for us,” Schaffer said..
Gene therapy first  took off in the 1990s. Early experiments including one that ended abruptly with the death of a pt, after he had an intense immune reaction were disappointing.. Now, the field seems to be going through a sort of renaissance, especiaily in treating diseases in the eye..The eye is often considered the easiest target for GT because it’s easily accessible - genetic material can be injected directly into the eye - & it’s also relatively cut off from the rest of the body, which means inserting a virus won’t set off an immune reaction.
Targeting the retina - Genetic mutations in  the eye usually are found in the cells located in or directly behind  the retina. In many cases  of hereditary blindness, the DNA mutation prevents the cells in the eye  from producing a protein that keeps them healthy.  But while the eye itself, is easily accessible to doctors, the cells in the back of the eye are difficult to reach. When doctors inject a virus carrying genetic materials into the white of the eye, most of the virus doesn’t make it to the retina, for reasons scientists don’t fully understand. They believe that viruses may be distracted along the way - possibly they’re attracted to  carbohydrates they run into before they reach  the retina. The viruses  basically stop to snack on the carbs & never make it any further.  Doctors can avoid this problem by injecting the  virus directly into the part of the retina where the genetic material is needed, but that poses problems. First, the procedure often causes a retinal detachment. Retinal detachments aren’t necessarily serious injuries in otherwise healthy eyes, but they can be harmful in pts whose retinas are degenerating. Second, the injection only gets the virus to a small pocket of the retina. Cells outside that pocket may not  get the virus or the genetic replacement material. But the newly engineered virus.. appears to overcome those problems.Early experiments have shown that when  the new virus is injected into the white of the eye, it drives straight to the retina & then spreads  throughout the tissue, where it delivers a payload of genetic material to the cells that need it. The team needs to do further testing in the lab & in animals before they can conduct human clinical trials with the new virus. They will start  first with pts with certain hereditary diseases that are known to  be caused by a single gene mutation...  ”We have to be careful - let’s not over-promise & under-deliver on GT,” said S Rose, Foundation Fighting Blindness  which provided funding to the UC Berkeley gene therapy studies. ”We’ve had problems  with that in the past, ”but certainly we’ve  come a long way, without a doubt.”  Erin Allda, SF Chronicle   Scanned/ocr correction/space edit - thl July 24, 2013

**ARVO- Association for Research in Vision & Oph 2013 meeting

%% Abbreviations:pt/pts - participant, patient, people; fup- follow-up; AMD-age-related macular degeneration; BCVA -best- corrected visual acuity; CNV - choroidal neovascularization [abnormal new vessels in choroid/ ‘wet’ part of wet AMD]  GA- Geographic Atrophy; OCT - optical coherence tomography; LCA - Leber congenital amaurosis; RCT randomized, controlled trial; RP- retinitis pigmentosa; RVO - retinal vein occlusion;RX-treatment,therapy
M-Medscape;MP - MedlinePlus; MPD-Med Page Today; MXP-Medical Express; JH- Johns Hopkins; Medical terms definition via Google meddictionaries. Excerpts compiled from sources including above & Pub Med & Oph Journals; [notes by THL] articles marked %% for searching.   Dawn Wilcox BSN RN, Coordinator The Health Library at Vista Center for the Blind &  Visually Impaired: an affiliate of Stanford Hospital Health Library. thl@vistacenter.org www.vistacenter.org


Nature 6/15 by David Cyranoski 

Biologists grow human-eye precursor from stem cells - Achievement raises hopes for optic repair in the clinic.  A stem-cell biologist has had an eye-opening success in his latest effort to mimic mammalian organ development in vitro. Yoshiki Sasai of the RIKEN Center for Developmental Biology (CBD) in Kobe, Japan, has grown the precursor of a human eye in the lab.
The structure, called an optic cup, is 550 micrometres in diameter and contains multiple layers of retinal cells including photoreceptors. The achievement has raised hopes that doctors may one day be able to repair damaged eyes in the clinic. But for researchers at the annual meeting of the International Society for Stem Cell Research in Japan  where Sasai presented the findings this week, the most exciting thing is that the optic cup developed its structure without guidance from Sasai and his team. 
The human eye is a complex structure — but the cues to build it come from inside the growing cells. Until recently, stem-cell biologists had been able to grow embryonic stem-cells only into two-dimensional sheets. But over the past 4years, Sasai has used mouse embryonic stem cells to grow well-organized, 3D cerebral-cortex, pituitary-gland and optic-cup tissue. His latest result marks the first time that anyone has managed a similar feat using human cells.
In Sasai’s experiment, retinal precursor cells spontaneously formed a ball of epithelial tissue cells and then bulged outwards to form a bubble called an eye vesicle. That pliable structure then folded back on itself to form a pouch, creating the optic cup with an outer wall (the retinal epithelium) and an inner wall comprising layers of retinal cells including photoreceptors, bipolar cells and ganglion cells. “This resolves a long debate,” says Sasai, over whether the development of the optic cup is driven by internal or external cues.  last month, a group in London showed that a transplant of stem-cell derived photo-receptors could rescue vision in mice. But the transplant involved only rods, not cones, and would leave the recipient seeing fuzzy images. Sasai’s organically layered structure offers hope that integrated photoreceptor tissue could one day be transplanted. The developmental process could also be adapted to treat a particular disease, & stocks of tissue could be created for transplant & frozen.
Sasai emphasizes that the cells in the optic cup are “pure”, unlike those in two-dimensional aggregates, which may still contain embryonic stem cells. This reduces concerns that transplants of such cells might develop cancerous growths or fragments of unrelated tissues. M Takahashi, has already started transferring sheets of the retina from such optic cups into mice. She plans to do the same with monkeys by the end of the year. The big question is whether transplanted tissue will integrate into native tissue. Clinicians and stem-cell biologists will also want to know just how easy it will be to repeat Sasai's success. Some at the meeting had already tried & failed to reproduce Sasai’s mouse experiment using human cells. “We need to know how robust, how reproducible it is,” says Austin Smith. director of  Centre for Stem Cell Research U Cambridge, UK
Nature doi:10.1038/nature.2012.10835 © 2012 Nature PubGroup, a division of Macmillan Publishers

Vision Research UpDate June 2012

Restoring sight with wireless implants A new type of retinal prosthesis – a combination of video goggles & photovoltaic retinal implants could make vision restoration more practicable. The development of retinal implants has been dogged by problems of unwieldiness since the first implantable stimulator for vision restoration was developed in 1968.  Sticking a mess of electronics, with wires, cables & inductive coils, into the human visual system was always going to be a tricky business.
J Loudin & his team at Stanford have developed a solution that overcomes many of these problems by the use of special goggles equipped with a miniature camera & a pocket PC designed to process the visual data stream. The resulting images would be displayed on a liquid crystal microdisplay embedded in the goggles, similar to what’s used in video goggles for gaming. Unlike regular video goggles the images would be beamed from the LCD using laser pulses of near- infrared light to a photovoltaic silicon chip - one-third as thin as a strand of hair - implanted beneath the retina. Electric currents from the photodiodes on the chip would then trigger signals in the retina, which then flow to the brain, enabling a pt to regain vision.  This simplifies what needs to be implanted & both transmits visual data & power directly to the implants, eliminating the need for a bulky external power source.   In order to explain how the set-up would work, Loudin regularly uses the Star Trek character Geordi LaForge as an analogy. “I'm not well versed in Star Trek any more, However, like his visor, our pts cannot see without the goggles.”

Loudin & team demonstrated the plausibility of their system by using rat retinas from both normal & blind rats.  The team placed an array of  photodiodes beneath the retinas & a multi-electrode array above the layer of ganglion cells to gauge the electric responses that are widely accepted indicators of visual activity. The team is now testing the system in live rats, taking both physiological & behavioral measure-ments, & are hoping to find a sponsor to support tests in humans. “It works like solar panels on your roof, converting light into electric current,” said D Palanker senior author. “But instead of the current flowing to your refrigerator, it flows into your retina.”

There are several other retinal prostheses being developed, & at least 2 in clinical trials-Second Sight (LA) & Retina Implant AG (Germany).  66 pts in Europe & US have already received existing retinal-implant systems. These multielectrode array implants which are interfaces that connect neurons to electronic circuitry, have restored some clarity of vision. But the surgery is complex & the implantation produces a range of unwanted side effects, including inflammation, & loss of neurons. Such systems are dependent on an external camera for retinal stimulation, so pts can’t use natural eye movements.  

Loudin's system reduces these problems because the implants are much thinner & wireless. The pulses deliver both visual information to the photovoltaic array & power it, reducing the number of components that need to be implanted. “Surgeons should be much happier with us. We’ve just got the one implant,” he says. The photo voltaic system also enables pts to scan the visual scene with their own eyes within the visual field of the goggles.
 E Zrenner Tübingen U, Germany, a leader in the field..says “It’s an elegant approach, It also allows for a high density of pixels, which means better resolution. The array is flexible, which allows larger arrays to be implanted.” He adds that while the current demonstra-tion is a convincing proof-of-concept, more work will be required on issues of biocompatibility, stability of the material & development of safe surgical procedures. He reckons that Loudin's implants will be available on the market within 1-2 years.  

The proposed prosthesis is intended to help people suffering from retinal degenerative diseases, such as AMD & RP.. In these diseases, the retina’s photoreceptor cells slowly degenerate, ultimately leading to blindness. But the inner retinal neurons that normally transmit signals from the photoreceptors to the brain are largely unscathed. Retinal prostheses are based on the idea that there are other ways to stimulate those neurons. The Stanford device uses near-infrared light, which has longer wavelength than normal visible light. “To make this work, we have to deliver a lot more light than normal vision would require,” said P. “And if we used visible light, it would be painfully bright.” Near-infrared light isn’t visible to the naked eye, though it is “visible” to the diodes that are implanted as part of this prosthetic system.

Compiled from 2 reports pub in AMD-Retina 5/2012 dw   Sources:i:10. 1038/nature.2012.10627 Loudin, J. et al. © 2012 Nature Pub Group. Funding by NIH. Air Force Office of Sci Research & Stanford’s Bio-X program & StanfordDepart of Oph, http://ophthalmology.stanford.edu/  © 2012 Stanford School of Medicine

From AMD-Retina Research List:

3/6 Usher Syndrome Gene Therapy Study Begins in Oregon  – The first-ever gene therapy for Usher syndrome, that causes both blindness & deafness, has moved into a Phase I/IIa clinical trial at Casey Eye Institute, Oregon Health & Science U. Developed by Oxford BioMedica a biopharm. company in the U.K. & a FFB partner, the UshStat® treatment is designed to halt vision loss in people affected with Usher syndrome type 1B, which is caused by defects in the MY07A gene. The team believes a single UshStat treatment may last several years, perhaps a lifetime. Success in the trial will open the door for using gene Rx  to treat other forms of Usher syndrome.” The treatment uses a re-engineered virus, to enable healthy copies of the MYO7A gene to penetrate the cells. The 2-year UshStat study will enroll 18 pts.  One eye of each pt will be injected with a tiny drop of liquid beneath the retina. The Ushtat Rx will be absorbed by retinal cells in a matter of hours.  The trial will evaluate the treatment’s safety as well as changes in retinal function of the treated eye versus the untreated eye.  Usher syndrome is the leading cause of combined deafness & blindness in the world. It affects approximately 45,000 people in the US. There are 3 primary types of Usher syndrome, designated by numerals, & 12 subtypes, designated by letters.StarGen™ the company’s gene Rx for Stargardt disease, is in a Phase I/IIa human study at OHSU & in Paris. The company’s RetinoStat®, a gene therapy for wet AMD is in a Phase I clinical study at Wilmer Eye Institute at Johns Hopkins Hospital  For more info, visit the clinical trials < www.blindness.org/... Source: sasi@acb.org

2/3/12 New Research Characterizes Glaucoma as a Neurologic Disorder Rather Than an Eye Disease -- A new paradigm to explain glaucoma [G] is rapidly emerging.. Some top researchers no longer think of G solely as an eye disease. Instead, they view it as a neurologic disorder that causes nerve cells to degenerate & die, similar to what occurs in Parkinson disease & Alzheimer's. Glaucoma is the most common cause of irreversible blindness worldwide. For many years, the prevailing theory was that vision damage in G was caused by abnormally high pressure inside the eye-IOP. As a result, lowering IOP was the only goal of those who developed surgical techniques & drugs to treat glaucoma. Today, a patient's IOP is no longer the only measurement the eye doctor uses to diagnose G, although it is still a key part of deciding how to care for the patient. Tracking changes in IOP over time informs the doctor whether the treatment plan is working. But even when surgery or medication successfully lowers IOP, vision loss continues in some patients. Also, some pts find it difficult to use eye drop meds as prescribed.  The new research focuses on the damage that occurs in a type of nerve cell called retinal ganglion cells (RGCs), which are vital to the ability to see. These cells connect the eye to the brain through the optic nerve. RGC-targeted glaucoma treatments now in clinical trials include: drugs injected into the eye that deliver survival & growth factors to RGCs; drugs known to be useful for stroke &  Alzheimer's, such as cytidine-5-diphosphocholine; & electrical stimulation of  RGCs, delivered via tiny electrodes implanted in contact lenses or other external devices. Human trials of stem cell therapies are in the planning stages. " As researchers turn their attention to the mechanisms that cause retinal ganglion cells to degenerate and die, they are discovering ways to protect, enhance & even regenerate these vital cells,  Scientists also hope that their in-depth exploration of RGCs will help them determine what factors, such as genetics, make some people more vulnerable to glaucoma. © 2012 American Academy Ophthalmology 

Dawn Wilcox RN Coordinator Health Library at Vista Center thl@vistacenter.org

 

From The Health Library monthly research lists:


1. Macular Degeneration Drug Being Tested In Sustained Release Implant - Lucentis is an effective drug for treatment of wet AMD. It is   injected into the back of the eye by a doctor about every 4-6 wks. Now a new device- a refillable drug port system - is in a safety trial. One end of the capsule-like device bathes the retina with the drug. The other end is an external port that allows doctors to periodically refill the drug supply. Genentech has predicted that doctor’s visits could be reduced to every 4 months for drug refills. Recruitment for a US trial may begin at the end of 2012, pending permission by the FDA. Source: AmHealthAss.Foundation 2/12


2. High Omega-3 Boosts Vitamin A Effect in Retinitis Pigmentosa - RP Eating oily fish such as salmon 2-3 times a week can improve the efficacy of daily vitA palmitate for delaying vision loss in patients with RP. Study found that in pts with RP who took an average of at least 0.20gram/day, annual distance visual acuity declined 40% slower & central visual field sensitivity almost 50% slower than in those with a diet low in those fatty acids. All of the pts were also taking 15,000 IU vitamin A/day. Dr.E.L.Berson said, "It is well known that if the retina does not have sufficient vitA, it will die. We & others have suggested that under daylight conditions, rods give cones vitA via Müller cells. [in retina] Release of vitamin A from its transport protein requires DHA, which is present in oily fish. This could explain why vitA plus an oily fish diet benefits pts with RP (more than vitA alone). The National Eye Institute sponsored Age-Related Eye Disease Study Research Group AREDS2 recently reported that there is also an association between dietary omega-3 intake & progression of AMD although an  randomized clinical trial is needed for definitive conclusions, ”dietary omega-3 intake is an easily modifiable factor that may influence the progression of retinal disease." Archives Oph. online 2/13/12


3. Do Glaucoma & Erectile Dysfunction Have a Common Cause?    Men with ED have a nearly 3-fold greater risk for also having open- angle glaucoma (OAG) than men with normal erectile function, report researchers. The study suggests that OAG and ED appear to have a common mechanism of endothelial dysfunction [in inner linning of blood vessels]. High blood sugar & insulin resistance, 2 primary components of the metabolic syndrome, also cause chronic inflammation which  in turn can damage vascular endothelia & lead to atherosclerosis. [hardening of the arteries] Ophthalmology. 2012;119:
4.Cell Abnormality Linked to Diabetic Retinopathy -  Indicator of vascular injury may be a useful biomarker. T1 pts with early retinopathy have abnormalities in their endothelial progenitor cells (EPC), a cell type released into the circulation as a result of vascular damage, [39pts] ADA 2/17
[from Monthly Health Library at Vista Center Research Lists Dawn Wilcox RN


12/7/11  Scientists at UCSB have developed a greater understanding of how the nervous system [includes the retina] becomes wired during early development. They examined the connectivity of nerve cells, called neurons, in mice retinas. Neurons communicate with one another via synapses where the dendrites & axon terminals of different cells form contacts. This is where nerve signals are transmitted from one neuron to another. The retina is an outgrowth of the brain during embryonic development, and is a precisely layered structure in which the cells and terminals are restricted to particular layers. The team studied a type of cone bipolar cell which relay information from cone photoreceptors to the retinal ganglion cells. The latter are neurons that in turn project information to the brain where further visual processing of the retinal image takes place. The total number of connections made by a cone bipolar cell was remarkably plastic, defined solely by the number of cone contacts formed. Studies like these may prove relevant for re-establishing connectivity following nerve cell..replacement in degenerative diseases, particularly as advances in stem cell biology make this an increasing possibility, the team says. Medical News Today

2. 12/12 Retina implant up date -- Several technologies to restore sight to retina-damaged eyes are making headway--one seeks to begin human trials in the U.S. & another has already hit the market in Europe. There is no effective treatment for RP, but researchers such as those at Retina Implant, AG, are making great strides to remedy this through implants that stimulate still active nerves in the retina, the layer of tissue at the back of the inner eye. RP kills the retina's photoreceptors, rod and cone cells that convert light into electrical signals, which are transmitted via the optic nerve to the brain's visual cortex for processing.  In November, Retina Implant, got approval to extend their phase II human clinical trial of its retinal implant outside its native Germany. Their implant is a 3- by 3-millimeter [mm]  microelectronic chip (0.1-mm thick), containing about 1,500 light- sensitive photodiodes, amplifiers & electrodes surgically inserted beneath the fovea (which contains the cone cells) in the retina's macula region. The fovea enables the clarity of vision that people rely on to read, watch TV & drive. The chip helps generate at least partial vision by stimulating intact nerve cells in the retina. The nervous impulses from these cells are then led via the optic nerve to the visual cortex where they finally lead to impressions of sight. Thus far, some patients report having a narrow field of vision partially restored, providing them with enough acuity to locate light sources such as windows and lamps as well as detect lighted objects against dark backgrounds. The chip's power source is positioned under the skin behind the ear & connected via a thin cable. Retina Implant has successfully placed chips beneath the retina of 9 pts since May 2010. The company hopes to widen patients' field of vision further by arranging 3 chips in a row beneath the retina. The ability to produce accurate colors via retinal implants, however, is very complicated & may not be possible for years. Retina Implant has also developed an outpatient Rx for early-stage RP called Okuvision, which  uses electric stimulation to help preserve retinal cells. The extension expands Retina Implant's trial to an additional 25 pts  beginning early next year & follows a partnership the company struck made with the Wills Eye Institute in Philadelphia. Wills is looking to become the lead U.S. clinical trial investigator site for Retina Implant's technology & to help the company through the US(FDA) review process.  SciAmerican  

3. 12/15 Needle-free, test being introduced to help Diabetics reduce their risk for serious complications – Young or old, any ethnic background, DM can hit anyone at anytime. Right now, 7 million diabetics are undiagnosed in the US. This new tool is a needle-free, test being introduced to help many pts reduce their risk for serious DM complications. Pediatric endocrinologist Dr. S.Chalews says the new tool uses light instead of an invasive skin biopsy to measure abnormal proteins in the skin associated with DM complications. This new machine could prove to be quicker & more effective than the presently used blood glucose testing machines. Two people with the same BS may have very different levels of glycated proteins. This new device is currently restricted to investigational use in the U.S. But it could get FDA approval by 2013. In other related news, USC neuroscientists have found the missing link on how the brain regulates blood sugar. They have identified the exact enzymes that lead to the release of glucose- controlling hormones. Understanding how the body naturally corrects for high or low blood sugar could change the way diabetes is treated.   Eyewitness News LA (KABC)

3-31-11 
From AMD-Retina Research List: 
3/28/11 US scientists have taken an important step towards using stem cells  to treat (AMD), The study demonstrates, for the first time, the ability to direct human iPS (induced pluripotent stem) cells to become the type of eye cells that die and cause loss of sight in sufferers of the disease. 'We have shown that we are able to generate retinal cells from cells originally taken from a small amount of biopsied skin, that are then induced to become stem cells', explained study leader at Georgetown U Med Centre Wash DC. .BioNews ..

'The retinal cells we have generated are really functional… they mimic the function of native retinal cells that play a key role in the eye for light absorption, nutrition & receptor function'. AMD affects the macula at the back of the eye, leading to death of retinal pigment epithelial (RPE) cells, a coloured layer which nourishes the light- receiving cells of the retina. Around 1 in 50 people more than 50 years of age, and up to one in 5 people over the age of 85, are affected by the disease, which results in the gradual loss of central vision needed for daily tasks such as reading and  driving...

While existing treatments slow the progression of AMD, there is currently no cure.  Human iPS cells offer the potential to use patient- specific stem cells to generate retinal cells for transplant. However, for transplantation to be possible, the iPS cells must first be programmed to possess the characteristics of native RPE cells The  authors were careful to stress that their work is preliminary and much future research is needed before these cells can be used clinically. They pointed out that the cells they produced also displayed some structural abnormalities & chromosome  damage, highlighting the need to focus on generating 'safe', as well as viable, iPS-derived cells. The study was published in the journal Stem Cells. BioNews 3/28/11

From the Diabetes Research List: 
The 3 Stages of Diabetic Retinopathy - In people with T1, mild abnormalities in the retina begin to appear an average of 7 years after diabetes begins, but damage that threatens vision usually does not develop until much later. In T2-- retinopathy may be present at the time of diagnosis or relatively soon afterward. This is because the onset of T2 is gradual; changes in the retina may have already taken place before diabetes   is even diagnosed. Here are the 3 progressive stages of Diabetic Retinopathy [DR]:..[link to more info]
 •  Microaneurysms- In the early, or nonproliferative, stages of DR, blood vessels in the retina develop weak spots that bulge outward (microaneurysms) & may leak fluid and blood into the surrounding retinal tissue. These initial abnormalities usually cause no visual symptoms & in many people the disease progresses no further. However, microaneurysms can lead to macular edema. •  Macular Edema  -- Swelling around the macula caused by the leakage & accumulation of fluid can occur in people with diabetes. The swelling alters the position of the retina & causes blurred vision. •  Proliferative Retinopathy  -- This is the most dangerous form of DR characterized by neovascularization -- the growth of new blood vessels onto the back surface of the vitreous humor. Acute loss of vision can occur when new blood vessels rupture & bleed into the vitreous humor or when these blood vessels lead to traction on the retina, causing it to detach from the back of the eye (retinal detachment). [Experts don't yet know exactly how high blood glucose levels cause DR. One possibility involves a protein known as vascular endothelial growth factor (VEGF), which promotes the growth of new blood vessels in the eye and is secreted into the eye in response to damage caused by diabetes. Studies suggest that elevated levels of cholesterol & triglycerides as well as high BP can increase the risk of diabetic retinopathy. These conditions are more common in people with DR than in the general population. Johns Hopkins 3/10/11

From Glaucoma- Optic Neuropathy Research List:
Eye Development Error Found To Be The Cause Of Cataracts, Glaucoma.  Research teams, working with juvenile cataracts in humans & with mice show that RNA granules can affect eye development & find a connection with glaucoma, They identified a malfunctioning gene (Tdrd7) in a mouse strain that develops both cataracts & glaucoma. Tdrd7, fails to build an essential protein & disrupts the development of the mouse eye lens. Mice missing the protein developed high IOP & optic nerve damage--the hallmarks of glaucoma--as well as cataracts... The missing protein belongs to a type of structure known as RNA granules which regulate mRNAs in the cell. mRNA serves as a template to carry DNA- encoded information from the nucleus into the body of the cell, providing the blueprints for protein production. Furthermore, the human patients developed glaucoma following cataract extraction. ..Tdrd7 deficiency greatly reduces the number of stress granules that are produced in lens cells in response to oxidative stress. Stress granules are important to protect the cell in stressful conditions. Oxidative stress has been previously suggested to contribute to glaucoma by damaging the ocular drainage structures. The new findings imply that mice & patients with these mutations may not have adequate protection from oxidative stress in the drainage structures of the eye. With increasing age, their tissues may be more susceptible to oxidative damage resulting in high intraocular pressure and glaucoma.  "There is a growing body of literature indicating that if you disturb oxygen levels in the eye– including after cataract surgery--the risk of developing glaucoma increases."  One author says that mutations in the Tdrd7 gene could cause a double jeopardy for childhood glaucoma.."This is a good example of a 21st century collaboration, with major contributions by multiple groups, including basic and clinical researchers across multiple continents." Funding included NEI.. Medical News Today 3/25/11

thl 3/31/11

From AMD-Retina :  ADA  2/11/11 Omega-3 fatty acids may help prevent retinopathy, which can lead to blindness.   Previous research has indicated that eye diseases may be slower to develop in people who eat a lot of fish. Now new research [Harvard]  suggests that an enzyme (5-LOX) may convert omega-3 into an acid called 4-HDHA, which slows abnormal blood vessel growth.  The team is working with the NEI to conduct a trial of omega-3 supplements in pts with advanced macular degeneration.

From the Diabetic Research List:  Diabetic Retinopathy [DR]- vasoregression [vessel deterioration] 3/2/11 Diabetes. 2011;60(1) DR is a sight-threatening, chronic microvascular [smallest blood vessels that bring oxygen & glucose to cells] a complication that eventually affects virtually all patients with diabetes.. The sight-threatening proliferative DR is not the primary response of the retina to chronic hyperglycemia [high blood sugar]  Rather, it is an attempted compensation for retinal hypoxia [lack of oxygen] caused by loss of capillary pericytes [normal cells in capillaries] & by formation of [abnormal non functional] capillaries ]  Further understanding  these mechanisms will provide new targets for drug intervention before irreversible retinal ischemia & proliferative retinopathy require damaging treatments such as panretinal laser ..

From the Glaucoma list:  M Long-term perimetric fluctuation in patients with different stages of glaucoma.  Pub 2/2011 AIM: To evaluate the long-term perimetric fluctuation (LF) in pts with different stages of glaucoma according to the Glaucoma Staging System 2. [161 eyes of 161 stable glauc pts; 4 Humphrey visual field tests] Conclusions - the lower the visual- field defect, the lower was LF, except at stage 5 . As test- retest changes exceeding LF could represent a sign of progression, the authors suggest that clinicians using this classification system calculate LF, in order to better differentiate true progression from variability.
compiled 3/11/11 D.Wilcox RN BSN Coordinator Health Library